Crystal form of asenapine maleate
View Patent ↗The invention relates to an orthorhombic crystal form of compound trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole (Z)-2-butenedioate, to methods for the preparation of this crystal form and to pharmaceutical compositions comprising an orthorhombic crystal form.
1. Orthorhombic trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (Z)-2-butenedioate isolated in a form which contains at least about 90 wt. % of the orthorhombic crystalline form.
2. The compound according to claim 1 which is characterized by an X-ray powder diffraction pattern obtained with CuKα radiation with peaks at values of 2-theta (2θ) of 10.5°, 15.7°, 18.3°, 19.0°, 22.2°, 23.2° and 27.5°.
3. The compound according to claim 1 which is characterized by an X-ray powder diffraction pattern obtained with CuKα radiation with peaks at values of 2-theta (2θ) of 10.5°, 15.7°, 18.3°, 19.0°, 20.3°, 20.8°, 22.2°, 23.2°, 25.6° and 27.5°.
4. The compound according to claim 1 which is characterized by a Raman spectroscopic pattern with peaks at values of 3051 cm −1 , 3029 cm −1 , 3011 cm −1 , 2888 cm −1 , 824 cm −1 and 717 cm −1 .
5. The compound according to claim 1 which is characterized by a Raman spectroscopic pattern with peaks at values of 3072 cm −1 , 3051 cm −1 , 3029 cm −1 , 3011 cm −1 , 2909 cm −1 , 2888 cm −1 , 1245 cm −1 , 824 cm −1 , 747 cm −1 , 717 cm −1 and 194 cm −1 .
6. A method of preparation of the compound according to claim 1 characterized in that trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole (Z)-2-butenedioate is crystallized from an ethanol/water mixture.
7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole (Z)-2-butenedioate in the orthorhombic crystal form, wherein said composition is prepared by using the trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (Z)-2-butenedioate of claim 1 .
8. A method of treating a mental disorder selected from schizophrenia and bipolar disorder in a mammal, comprising administering a therapeutically effective amount of a composition of claim 7 .
9. The method according to claim 8 , wherein the mammal is a human.
10. Then method according to claim 8 , wherein the mental disorder is schizophrenia.
11. The method according to claim 8 , wherein the mental disorder is bipolar disorder.